Abstract: A polypeptide and polynucleotides encoding same comprising one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to an amino terminus of a cytokine and two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a carboxy terminus of a cytokine are disclosed. Pharmaceutical compositions comprising the polypeptide and polynucleotides of the invention and methods of using same are also disclosed.

Abstract: The present invention relates to novel expression cassettes and vectors for efficiently producing authentic recombinant human proteins from stable cultures of novel human cell lines, the authentic recombinant proteins produced therefrom, and antibodies raised against those authentic recombinant proteins.

Abstract: Derivatives of PSAs are synthesised, in which a reducing and/or non-reducing end terminal sialic acid unit is transformed into a N-hydroxysuccinimide (NHS) group. The derivatives may be reacted with substrates, for instance substrates containing amine or hydrazine groups, to form non-cross-linked/crosslinked polysialylated compounds. The substrates may, for instance, be therapeutically useful drugs, peptides or proteins or drug delivery systems.

Abstract: A process of purifying a Growth Factor Protein in a purification sequence employing chromatography characterized in that at least one chromatography is performed using a multimodal resin the Growth Factor Protein binds to the multimodal resin at a pH between 4 to 6.2, and the Growth Factor Protein is eluting at a pH>6.3, and the elution of Growth Factor Protein is improved by addition of arginine and/or NaCl to the eluting buffer. The multimodal resin step is followed by a yeast derived affinity ligand resin step, which results of a purity of the product>90%.

Abstract: The invention provides a modified glycosylation-deficient HGF and a production method thereof. The glycosylation-deficient HGF is produced by introducing amino acid mutation(s) so that no glycosylation take place at at least one glycosylation site of hepatocyte growth factor.

Abstract: A promoter for transformation of a plant, in particular an aboveground organ specific promoter, a recombinant plant expression vector including the promoter, a method of producing target protein using the recombinant plant expression vector, target protein produced by the method, a method of producing a transformed plant using the recombinant plant expression vector, a transformed plant produced by the same, and a seed of the plant.

Abstract: The invention provides multivalent ligand binding agents (traps) for members of the TGF-? superfamily and polypeptide linkers and methods for making and using such constructs. The traps may be used as therapeutic or diagnostic (imaging or non-imaging) agents for diseases/disorders caused by over-production/activity of the target ligand. In an embodiment of the invention there is provided a multivalent binding agent with affinity for a member of the TGF-? superfamily, the agent having the general structure I: (<bd1>-linker1)k-[{<bd1>-linker2-<bd2>-linker3f-}n-(<bd3>)m-(linker4-<bd4>)d]h, where: n and h are independently greater than or equal to 1; d, f, m and k are independently equal to or greater than zero; bd's are polypeptide binding domains having an affinity for the same member of the TGF-? superfamily; and, linkers are unstructured polypeptide sequences.

Abstract: The invention relates to truncated growth factors and variants thereof. The invention also relates to methods of making and using the truncated growth factors.

Abstract: The invention provides multivalent ligand binding agents (traps) for members of the TGF-? superfamily and polypeptide linkers and methods for making and using such constructs. The traps may be used as therapeutic or diagnostic (imaging or non-imaging) agents for diseases/disorders caused by over-production/activity of the target ligand. In an embodiment of the invention there is provided a multivalent binding agent with affinity for a member of the TGF-? superfamily, the agent having the general structure I: (<bd1>linker1)k-[{<bd1>-linker2-<bd2>linker3f-}n-(<bd3>)m-(linker4-<bd4>)d]h, where: n and h are independently greater than or equal to 1; d, f, m and k are independently equal to or greater than zero; bd's are polypeptide binding domains having an affinity for the same member of the TGF-? superfamily; and, linkers are unstructured polypeptide sequences.

Abstract: This present invention relates to pharmacologically potent and/or stable variants of human fibroblast growth factor 21 (FGF21), pharmaceutical compositions comprising FGF21 variants, and methods for treating type 2 diabetes, obesity, dyslipidemia, or metabolic syndrome, or any combination thereof, using such variants.

Abstract: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: In general, the invention features substantially purified MANF and substantially purified nucleic acids encoding the same. The invention also features a pharmaceutical composition that includes MANF and a pharmaceutically-acceptable excipient, methods for treatment of a neurodegenerative disease, methods for improving dopaminergic neuronal survival during or following cell transplantation, methods for production of neurons for transplantation, and methods for identifying compounds that modulate or mimic MANF's biological activity.

Abstract: The present invention relates to fusion proteins comprising an antibody, functional fragment or functional derivative thereof having specific binding affinity to either the extracellular domain of oncofetal fibronectin (ED-B) or at least one of the extracellular domains of oncofetal tenascin fused to a cytokine selected from the group consisting of IL-10, IL15, IL-24 and GM-CSF, functional fragments and functional derivatives thereof. The invention is also directed to the use of at least one of said fusion proteins for the manufacture of a medicament. In particular, the invention concerns the use of said medicament for the treatment of tumors or chronic inflammatory diseases such as atherosclerosis, arthritis and psoriasis.

Abstract: This invention relates to modified IGF-II binding domains of the Insulin-like Growth Factor 2 Receptor (IGF2R) which have enhanced binding affinity for IGF-II relative to the wild type IGF-II binding domain. Suitable IGF-II binding domains may be modified, for example, by substituting residue E1544 for a non-acidic residue. These modified domains may be useful in the sequestration of Insulin-like Growth Factor II (IGF-II), for example, in the treatment of cancer.

Abstract: A method of selectively introducing a substituent into a protein proximal to a binding site on the protein for a homing peptide, comprising: (a) contacting the protein with a compound comprising a homing peptide having the ability to bind to the binding site of the protein; and (b) allowing a moiety on the protein proximal to the binding site to react with the compound comprising the homing peptide, thereby to transfer the substituent G onto the protein.

Abstract: A composition of matter is disclosed which comprises isolated oligomers of human islet amyloid polypeptide (IAPP). Antibodies recognizing same are also disclosed. Use of the composition of matter and the antibodies are also disclosed.

Abstract: The present invention relates to a biosynthetic random coil polypeptide or a biosynthetic random coil polypeptide segment or biosynthetic conjugate, wherein said biosynthetic random coil polypeptide, said biosynthetic random coil polypeptide segment or said biosynthetic conjugate comprises an amino acid sequence consisting solely of proline and alanine amino acid residues, wherein said amino acid sequence consists of at least about 50 proline (Pro) and alanine (Ala) amino acid residues. Said at least about 50 proline (Pro) and alanine (Ala) amino acid residues may be (a) constituent(s) of a heterologous polypeptide or an heterologous polypeptide construct. Also uses and methods of use of these biosynthetic random coil polypeptides or polypeptide segments or said conjugates are described.

Abstract: The present invention relates to a method for purifying a protein belonging to the TGF-?, superfamily, preferably BMP, and more preferably BMP-2. According to the invention, the number of purification steps is reduced and the purification process is simplified, compared to the conventional BMP-2 purification method. Thus, the time required for purification can be shortened and the cost can be reduced. In addition, the invention solves the problem that as the time for purification increases and the number of purification steps increases, BMP-2 is degraded by protease or lost during purification steps, resulting in a decrease in the final yield of BMP-2. Thus, the invention increases the final yield of BMP-2.

Abstract: The invention relates to an isolated amino acid that can act as an antagonist to FGF signaling, comprising at least a portion of the FGF protein amino acid sequence, and including a mutation in either a) the integrin ?v?3 binding region of FGF-1; or b) the FGFR binding region of FGF-1.

Abstract: A process is described for producing a polypeptide heterologous to E. coli wherein E. coli cells comprising nucleic acid encoding the polypeptide are cultured in a culture medium while feeding to the culture medium a transportable organophosphate, such that the nucleic acid is expressed. The polypeptide is then recovered from the cells.

Abstract: A method of treating or preventing an ovary-related syndrome associated with infertility in a subject in need thereof is provided. The method comprising administering to the subject a pharmaceutical composition comprising an active ingredient consisting of pigment epithelium-derived factor (PEDF) and a pharmaceutically acceptable carrier, thereby treating or preventing the ovary-related syndrome associated with infertility in the subject.

Abstract: The present invention refers to a fusion protein comprising a TNF-superfamily (TNFSF) cytokine or a receptor binding domain thereof fused to a collectin trimerization domain, to a nucleic acid molecule encoding the fusion protein, and to a cell comprising the nucleic acid molecule. The fusion protein is present as a trimeric complex or as an oligomer thereof. The fusion protein, the nucleic acid, and the cell is suitable as pharmaceutical composition or for therapeutic, diagnostic and/or research applications.

Abstract: Provided is a peptide including the following amino acid sequence. Tyr-Xaa0-Xaa1-Tyr-Tyr-Xaa2-Xaa3-Tyr-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11 (SEQ ID NO: 4: wherein Xaa0, Xaa1, Xaa2, Xaa3, Xaa4, Xaa5, Xaa6, Xaa7, Xaa8, Xaa9, Xaa10 and Xaa11 represent any amino acid) or Tyr-Asn-Asp-Tyr-Tyr-Tyr-Tyr-Cys-Tyr-Arg-Asp-Tyr-Asp (SEQ ID NO: 20).

Abstract: The present invention provides dyes, reactive dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins and nucleic acids. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes are also provided that comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been modified by the addition of charged and polar groups to provide beneficial properties.

Abstract: An object of the present invention is to provide a method for detecting cancer through identification of genes exhibiting characteristic behavior in the cases of cancer such as ovarian cancer, and a cell growth inhibitor. The present invention provides a method for detecting cancer, which comprises detecting canceration including malignancy of a specimen through detection of at least one alteration of a gene existing in a chromosomal region 2q14. 2, 3p24. 1, 3q26. 2, 3q29, 4q34. 2, 6q23, 9p21. 3, 11q13. 3, 13q22.1, 13q33. 1, 13q33. 3, 15q12, 15q15. 1, 17p12, 17p13. 1, 17p13. 3, 18q21. 1, 18q21. 2, 18q21. 31, 18q21. 32, 18q21. 33, 18q23, 20q13. 13, 20q13. 2, 20q13. 31, 20q13. 33, Xp11. 23, Xp13.1, Xp13. 3, Xp26. 2, Xp26. 3, or Xq28 in the specimen.

Abstract: Compounds useful as labels with properties comparable to known fluorescent compounds. The compounds are conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

Abstract: The present invention is directed to a method for producing a biomolecule conjugate where the method is integrated into a single unit operation.

Abstract: The present invention relates to growth hormone (GH) compounds having additional disulphide bridges and at least one additional single point mutation making the compounds resistant to proteolytic degradation.

Abstract: A discovery process beginning with an in vivo screening of proteins, peptides, natural products, classical medicinal compound or other substances. The administration of compounds to the animal can be either direct or indirect, such as by the administration and expression of cDNA-containing plasmids. Since the discovery process of the invention is based on a non-preconceived hypothesis and whole organism multi-organ analysis, a compound can be selected for testing in the absence of any biological selection criteria. The resulting organism-wide pattern of the gene expression changes in the transcriptome provides an overview of the activities at the molecular and organism-wide levels. The discovery process of the invention then integrates in vivo profiling and internal and external genomic databases to elucidate the function of unknown proteins, typically within few months.

Abstract: Novel polypeptide derivatives having protracted profile of action.

Abstract: A chimeric therapeutic polypeptide of a pre-existing therapeutic polypeptide is disclosed, as are a method of enhancing folded stabilization and a pharmaceutical composition of the glycosylated chimer. The pre-existing and chimeric polypeptides have substantially the same length, substantially the same amino acid residue sequence, and exhibit at least one tight turn containing a sequence of four to about seven amino acid residues in which at least two amino acid side chains extend on the same side of the tight turn and are within less than about 7 ? of each other. The chimeric therapeutic polypeptide has the sequon Aro-(Xxx)n-(Zzz)p-Asn-Yyy-Thr/Ser (SEQ ID NO:001) within that tight turn sequence such that the side chains of the Aro, Asn and Thr/Ser amino acid residues project on the same side of the turn and are within less than about 7 ? of each other. That sequon is absent from the pre-existing therapeutic polypeptide.

Abstract: CXCL9 promotes bone marrow regeneration, increases peripheral white blood cells, and increases survival if administered prior to treatment of a subject with chemotherapeutic drugs such as 5-FU or radiotherapy. Similar effects are obtained by administering an anti-CXCL9 antibody following chemotherapy or radiotherapy. Compositions and methods are presented for the treatment of cancer and bone marrow diseases.

Abstract: Procedure for obtaining a composition that contains growth factors, which comprises the steps of heat-treating a platelet-rich plasma or the supernatant of a platelet-rich plasma that contains released growth factors in order to increase its temperature, for eliminating the complement and reducing the immunoglobulins present therein, and lyophilizing the plasma or supernatant in order to obtain a final dry composition that can easily be transported, handled and stored, thereby facilitating periodic or chronic treatments with blood compounds. It has been shown that when the final dry composition is resuspended, a once again humid composition is obtained that maintains its biological properties intact.

Abstract: Provided are a hepatopoietin PCn (HPPCn) and its homologous proteins, which can promote hepatocyte proliferation in vitro, promote liver regeneration in vivo, inhibit the growth of tumor cells and promote the apoptosis of tumor cells. The hepatopoietin PCn (HPPCn) and its homologous proteins are useful for the treatment of acute and chronic liver injury, or the treatment of liver fibrosis.

Abstract: The present invention provides modulators of TNF, particularly peptides and their derivatives, particularly GEP peptides, which antagonize TNF and TNF-mediated responses, activity or signaling. The invention provides methods of antagonizing TNF and the modulation of TNF-mediated diseases or responses, including inflammatory diseases and conditions. Compositions of GEP peptides, including in combination with other inflammatory mediators, are provided. Methods of treatment, alleviation, or prevention of TNF-mediated diseases and inflammatory conditions, including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, inflammatory bowel diseases, Chrohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, are provided.

Abstract: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.

Abstract: We disclose growth hormone [GH] fusion proteins that have increased in vivo stability and activity; nucleic acid molecules encoding said proteins and methods of treatment of growth hormone deficiency that use said fusion proteins. The GH fusion proteins comprise human GH covalently linked to the extracellular domain of Growth Hormone Receptor [GHR] either as a direct in-frame translational fusion or via a flexible peptide linker. The GH/GHR fusion proteins have exceptional pharmacokinetics and are potent growth hormone receptor agonists. The GH/GHR fusion proteins form head to tail dimers.

Abstract: The invention relates to variants and fusions of fibroblast growth factor 19 (FGF19), variants and fusions of fibroblast growth factor 21 (FGF21), fusions of fibroblast growth factor 19 (FGF19) and/or fibroblast growth factor 21 (FGF21), and variants or fusions of fibroblast growth factor 19 (FGF19) and/or fibroblast growth factor 21 (FGF21) proteins and peptide sequences (and peptidomimetics), having one or more activities, such as glucose lowering activity, and methods for and uses in treatment of hyperglycemia and other disorders.

Abstract: There is disclosed a molecular composition(s) of a novel tissue protective erythropoietin (EPO) binding receptor protein complex, termed NEPOR. Presence of NEPOR components on a tumor allows EPO to impinge on the survival of associated cells thereby enhancing tumor progression and negatively effecting patient survival. Presence of NEPOR represents a prognostic biomarker for poorer patient outcome. Thus, methods are provided for stratifying patients having a tumor as suitable (i.e. NEPOR not present) or non-suitable (i.e., NEPOR present) for EPO treatment, comprising: (a) isolating a tissue sample from an individual who is receiving or is a candidate for receiving erythropoietin, (b) determining the level of expression of the NEPOR gene(s) (mRNA) and/or the presence of the NEPOR gene product (protein) from the isolated tissue, and (c) correlating the presence of an NEPOR gene expression product or the presence of NEPOR protein to a physiological response to the treatment with erythropoietin.

Abstract: Multimeric protein structures are disclosed herein, as well a process for preparing same, and methods employing same for treating various diseases or disorders. The multimeric protein structures comprise at least two monomers of a therapeutic protein, including a TNF-alpha, a luteinizing hormone, an immunoglobin, a TNF-alpha receptor, a CTLA-4, a urate oxidase, a VEGF, a PDGF, a VEGF receptor, a PDGF receptor, an interleukin-17, and/or fragments thereof, the monomers being covalently linked to one another via a linking moiety. The multimeric protein structures exhibit improved performance as compared to the corresponding native proteins, including a longer lasting activity in vivo.

Abstract: The present invention provides a method for purification of a protein that is conjugated to an albumin binding moiety from a mixture comprising (i) said protein in said conjugated form and (ii) said protein in a form that is not conjugated to said albumin-binding moiety, the method comprising: (a) providing a solid support comprising a substance capable of specifically binding to the albumin binding moiety; (b) contacting said solid support of (a) with said mixture comprising protein and conjugated protein under suitable conditions for binding of the albumin binding moiety to the substance as defined in (a); and (c) eluting components bound to the solid support.

Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.

Abstract: Scaffold comprises a polymer defining macropores and comprising hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, which is crosslinked through the self-crosslinkable group. The macropores have an average pore size larger than 50 microns and are at least partially interconnected. In one method, bicontinuous emulsion comprising a continuous aqueous phase and a continuous polymer phase is formed. The polymer phase comprises hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, and is crosslinked through the self-crosslinkable group to form a polymer defining at least partially interconnected pores. In another method, phase separation is induced in a solution comprising a polymer precursor and water to form a bicontinuous emulsion comprising a continuous polymer phase and a continuous aqueous phase.

Abstract: Expression of FGF21 in a S. cerevisiae pmt2 knock out strain reduces the O-glycosylation significantly and does not decrease the expression level. Expression in mkc7 knock out strain can decrease degradation of FGF21 and analogues thereof. Point mutations at position R17 and R36 can decrease degradation of FGF21 and analogues thereof when they are expressed in yeast.

Abstract: The present invention provides peptides that home to a joint of an animal, wherein said peptide comprises an amino acid motif selected from the group consisting of NQR and ADK. Also provided are methods of treating a subject having an arthritic joint, comprising the step of administering to said subject a pharmacologically effective dose of a composition provided herein.

Abstract: We describe modified growth hormone fusion proteins and dimers comprising said fusion proteins; nucleic acid molecules encoding said proteins and methods of treatment that use said proteins in the treatment of conditions that result from growth hormone excess.

Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one aromatic amine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one alkylated amine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: An effective agent for treating ischemic disease, the agent containing human granulocyte colony-stimulating factor (human G-CSF) as an active ingredient is disclosed. By administering this therapeutic agent, an effective therapy particularly for obstructive arteriosclerosis is provided which can eliminate drawbacks with conventional therapies, such as kinesitherapy, pharmacotherapy, and revascularization, and recently proposed therapies, such as gene therapy and intramuscular transplantation of bone marrow cells. Furthermore, the therapeutic agent can be used as an agent for treating ischemic disease, such as ischemic cerebrovascular disorder or ischemic heart disease.

Abstract: The invention discloses a combined preparation containing IL-10 and rapamycin, able to induce immunosuppression and antigen-specific immune tolerance, and the use thereof in the treatment of diseases involving an excessive, dysfunctional or uncontrolled immune responses mediated by T cells.

Abstract: A stable aqueous composition containing follicle-stimulating hormone, which comprises follicle-stimulating hormone and histidine as a stabilizing agent.